Osteoporosis, the Elderly and Fractures

Osteoporosis
•	In osteoporosis, cortical bone and bone trabeculae are thinned and decreased in number, leading to a decrease in bone mass but no distortion in the bone's architecture.
•	Bone pain especially in the back is common with compression fracture of the vertebral bodies. Uneven compression makes the old person shorter and more hunched up - the spine bends anteroposteriorly (kyphosis).
•	Osteoporosis is common in the elderly and they are prone to fractures to neck of the femur and wrists from relatively trivial injuries like a fall. In extreme cases, sometimes bones may be broken in bed as they try to turn round against the resistance of bedclothes (yuck!). 
•	Fractures in the neck of the femur are important in that they are so common and take up a lot of the workload. (It also costs a lot of money.)
•	Senile osteoporosis occurs especially in post-menopausal women and oestrogen is important.
•	Disuse can also lead to osteoporosis especially if your limb is paralysed or if your limb has to be immobilised after you've broken it.
•	Prolonged corticosteroid therapy can also cause osteoporosis.

Kyphosis
•	As we get older our nucleus pulposus (the squishy bit in the middle of our vertebral discs) becomes more dehydrated (less squishy). Eventually, the whole disc can become affected and collapses. This might happen more often in the lower back, which takes up most of the load.
•	In elderly people, the postural muscles also weaken, making them more likely to bend their backs.
•	The loss in muscle mass is age-related and may be due to the lowering in the capacity of the mitochondria to get on with oxidative phosphorylation. On top of that, the elderly tend to take things easy and sit at home rather than taking up exercise. This aggravates the drop in muscle mass and strength. (Notice that the size of the muscle cells shrink rather than the actual numbers.)
•	When you put a limb into a cast, the muscle may atrophy unless exercised, and this is especially the case with the quadriceps femoris.

Fracture
The lecture pretty much summed up bone fracture healing, so I'll not bother you with a mega boring account of it all. Here's a quick reminder of the steps instead:
1.	Haematoma formation 
2.	Organisation of haematoma: cells involved are neutrophils, macrophages and fibroblasts. They're helped by platelet derived growth factor (PDGF), transforming growth factor ß (TGF-ß) and fibroblast growth factor (FGF).
3.	Osteoblast production and migration: the cortex lays down woven bone and the external callus produces cartilage.
4.	Bony union by woven bone: by this time - after 3rd week - the callus is well established (cartilage is replaced by woven bone) and remodelling by osteoclasts takes place to remove excess callus.
5.	Woven bone remodelled: the woven bone is replaced by lamellar trabecular bone (the trabeculae orientate to lines of stress).

Factors that can delay healing
  poor blood supply
  poor general nutritional status
  poor apposition of fractured bone ends	  presence of foreign bodies
  presence of infection
  corticosteroid therapy	

When the elderly fracture their bones, the things heal more slowly than in younger folk. (When I say the 'things', I meant the bones - though the elderly do heal more slowly too…) The factors featuring most prominently in this case are:
•	Decreased mobility - the delay in healing caused by this can lead to wasting of the muscles as well, which would decrease mobility even further.
•	Cells can't multiply as well as they used to.  "Eh, if I were a couple of years younger, I'd show you a thing or three!"
•	Impaired blood supply. "Bah! They don't make 'em like they used to."
•	Diet deficiency - minerals, trace elements and vitamins - "Damn it, just give me my bread and my Lurpak ™ and I'll be as fit as a fiddle."

Disodium Etidronate (p 606 Katzung)
•	This is a biphosphonate. It's an analogue of pyrophosphate but it's harder to break down.
•	It's adsorbed onto bone crystals (which are known affectionately as hydroxyapatite). This effectively prevents both growth and breakdown of the crystals - decreasing overall bone turnover. In addition, the osteoclasts that phagocytose these crystals seem to have enough and not eat any more.
•	Being incorporated into bone effectively increases its half-life (which depends ultimately on the bone turnover rate!).
•	1-10% of it is absorbed in the gut and 50% of that finds its way into bone. The other half is excreted unchanged in the urine. All in all, it's a relatively non-toxic drug.
•	Other effects that we know about with this drug are: it inhibits 1,25(OH)2 D production, intestinal calcium transport, and bone cell glycolysis and growth; there are changes in acid and alkaline phosphatases too. 
•	Clinical trials are still undergoing to see if it actually encourages bone to grow back (oestrogen therapy only stops bone loss).
•	Calcium is in itself only a weak inhibitor of bone resorption. Used cyclically with disodium etidronate, it has been shown to reduce the incidence of osteoporotic fractures.

Oestrogen
•	This is the best agent used in osteoporosis as it stops the process by reducing bone resorption. Progesterone has been shown to increase bone formation but its effects have been less beneficial than with oestrogen. They are commonly used in combination as this reduces the risk of endometrial cancer (compared to using oestrogen alone).
•	The current theory is that oestrogen helps keep the levels of interleukin-1 (IL-1) down. Scientists think that after menopause the lowering of oestrogen makes the blood monocytes secrete more IL-1. This activates osteoclasts and causes them to step up breakdown of bone. The osteoblasts can't keep up with the breakdown (they do try, though) and so the bones start to lose material and become weaker. Ganong (p355 in the 17th Edition) has a table of the factors that stimulate/inhibit osteoblasts/osteoclasts.

Bendrofluazide is a thiazide diuretic. It has a beneficial effect on bone in that it reduces renal calcium excretion by increasing calcium reabsorption in the kidney. More calcium means less bone breakdown and Katzung says that this is how thiazides increase the effectiveness of parathyroid hormone (PTH).

"Don't confuse intelligence and wisdom. Intelligence tells you 
it's raining, but it's wisdom that tells you to get out of it!"
-	Explains why even the most seemingly intelligent of us can make the most fantastic cock-ups. (The important thing though, is to learn from them!)